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15. Management of Diabetes in
Pregnancy: Standards of Medical
Care in Diabetes—2022
Diabetes Care 2022;45(Suppl. 1):S232–S243 | https://doi.org/10.2337/dc22-S015
American Diabetes Association
Professional Practice Committee*
The American Diabetes Association (ADA) “Standards of Medical Care in Dia-
betes” includes the ADA’s current clinical practice recommendations and is
intended to provide the components of diabetes care, general treatment goals
and guidelines, and tools to evaluate quality of care. Members of the ADA Profes-
sional Practice Committee, a multidisciplinary expert committee (https://doi
.org/10.2337/dc22-SPPC), are responsible for updating the Standards of Care
annually, or more frequently as warranted. For a detailed description of ADA
standards, statements, and reports, as well as the evidence-grading system for
ADA’s clinical practice recommendations, please refer to the Standards of
Care Introduction (https://doi.org/10.2337/dc22-SINT). Readers who wish to
comment on the Standards of Care are invited to do so at professional
.diabetes.org/SOC.
DIABETES IN PREGNANCY
The prevalence of diabetes in pregnancy has been increasing in the U.S. in parallel
with the worldwide epidemic of obesity. Not only is the prevalence of type 1 diabe-
tes and type 2 diabetes increasing in women of reproductive age, but there is also
a dramatic increase in the reported rates of gestational diabetes mellitus (GDM).
Diabetes confers significantly greater maternal and fetal risk largely related to the
degree of hyperglycemia but also related to chronic complications and comorbid-
ities of diabetes. In general, specific risks of diabetes in pregnancy include sponta-
neous abortion, fetal anomalies, preeclampsia, fetal demise, macrosomia, neonatal
hypoglycemia, hyperbilirubinemia, and neonatal respiratory distress syndrome,
among others. In addition, diabetes in pregnancy may increase the risk of obesity,
hypertension, and type 2 diabetes in offspring later in life (1,2).
PRECONCEPTION COUNSELING
Recommendations
15.1 Starting at puberty and continuing in all women with diabetes and
reproductive potential, preconception counseling should be incorpo-
rated into routine diabetes care. A
15.2 Family planning should be discussed, and effective contraception (with
consideration of long-acting, reversible contraception) should be pre-
scribed and used until a woman’s treatment regimen and A1C are opti-
mized for pregnancy. A
15.3 Preconception counseling should address the importance of achieving
glucose levels as close to normal as is safely possible, ideally A1C <6.5%
*A complete list of members of the American
Diabetes Association Professional Practice Com-
mittee can be found at https://doi.org/10.2337/
dc22-SPPC.
Suggested citation: American Diabetes Asso-
ciation Professional Practice Committee. 15.
Management of diabetes in pregnancy: Stan-
dards of Medical Care in Diabetes—2022.
Diabetes Care 2022;45(Suppl. 1):S232–S243
© 2021 by the American Diabetes Association.
Readers may use this article as long as the
work is properly cited, the use is educational
and not for profit, and the work is not altered.
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https://professional.diabetes.org/SOC
https://doi.org/10.2337/dc22-SPPC
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(48 mmol/mol), to reduce the
risk of congenital anomalies,
preeclampsia, macrosomia, pre-
term birth, and other complica-
tions. A
All women of childbearing age with dia-
betes should be informed about the
importance of achieving and maintaining
as near euglycemia as safely possible
prior to conception and throughout preg-
nancy. Observational studies show an
increased risk of diabetic embryopathy,
especially anencephaly, microcephaly,
congenital heart disease, renal anomalies,
and caudal regression, directly propor-
tional to elevations in A1C during the first
10 weeks of pregnancy (3). Although
observational studies are confounded by
the association between elevated peri-
conceptional A1C and other poor self-
care behavior, the quantity and consis-
tency of data are convincing and support
the recommendation to optimize glyce-
mia prior to conception, given that
organogenesis occurs primarily at 5–8
weeks of gestation, with an A1C <6.5%
(48 mmol/mol) being associated with the
lowest risk of congenital anomalies, pre-
eclampsia, and preterm birth (3–7). A
systematic review and meta-analysis of
observational studies of preconception
care for women with preexisting diabetes
demonstrated lower A1C and reduced
risk of birth defects, preterm delivery,
perinatal mortality, small-for-gestational-
age births, and neonatal intensive care
unit admission (8).
There are opportunities to educate
all women and adolescents of reproduc-
tive age with diabetes about the risks of
unplanned pregnancies and about
improved maternal and fetal outcomes
with pregnancy planning (9). Effective
preconception counseling could avert
substantial health and associated cost
burdens in offspring (10). Family plan-
ning should be discussed, including the
benefits of long-acting, reversible con-
traception, and effective contraception
should be prescribed and used until a
woman is prepared and ready to
become pregnant (11–15).
To minimize the occurrence of compli-
cations, beginning at the onset of puberty
or at diagnosis, all girls and women with
diabetes of childbearing potential should
receive education about 1) the risks of
malformations associated with unplanned
pregnancies and even mild hyperglycemia
and 2) the use of effective contraception
at all times when preventing a pregnancy.
Preconception counseling using develop-
mentally appropriate educational tools
enables adolescent girls to make well-
informed decisions (9). Preconception
counseling resources tailored for adoles-
cents are available at no cost through the
American Diabetes Association (ADA)
(16).
Preconception Care
Recommendations
15.4 Women with preexisting dia-
betes who are planning a
pregnancy should ideally be
managed beginning in precon-
ception in a multidisciplinary
clinic including an endocrino-
logist, maternal-fetal medicine
specialist, registered dietitian
nutritionist, and diabetes care
and education specialist, when
available. B
15.5 In addition to focused atten-
tion on achieving glycemic tar-
gets A, standard preconception
care should be augmented with
extra focus on nutrition, diabetes
education, and screening for dia-
betes comorbidities and compli-
cations. E
15.6 Women with preexisting type
1 or type 2 diabetes who are
planning pregnancy or who
have become pregnant should
be counseled on the risk of
development and/or progres-
sion of diabetic retinopathy.
Dilated eye examinations should
occur ideally before pregnancy
or in the first trimester, and
then patients should be moni-
tored every trimester and for 1
year postpartum as indicated
by the degree of retinopathy
and as recommended by the
eye care provider. B
The importance of preconception care
for all women is highlighted by the Amer-
ican College of Obstetricians and Gyne-
cologists (ACOG) Committee Opinion
762, “Prepregnancy Counseling” (17). A
key point is the need to incorporate a
question about a woman’s plans for
pregnancy into routine primary and gyne-
cologic care. The preconception care of
women with diabetes should include the
standard screenings and care recom-
mended for all women planning preg-nancy (17). Prescription of prenatal
vitamins (with at least 400 mg of folic
acid and 150 mg of potassium iodide
[18]) is recommended prior to concep-
tion. Review and counseling on the use
of nicotine products, alcohol, and recrea-
tional drugs, including marijuana, is
important. Standard care includes screen-
ing for sexually transmitted diseases and
thyroid disease, recommended vaccina-
tions, routine genetic screening, a careful
review of all prescription and nonpre-
scription medications and supplements
used, and a review of travel history and
plans with special attention to areas
known to have Zika virus, as outlined by
ACOG. See Table 15.1 for additional
details on elements of preconception
care (17,19). Counseling on the specific
risks of obesity in pregnancy and lifestyle
interventions to prevent and treat obe-
sity, including referral to a registered
dietitian nutritionist (RD/RDN), is recom-
mended when indicated.
Diabetes-specific counseling should
include an explanation of the risks to
mother and fetus related to pregnancy
and the ways to reduce risk, including
glycemic goal setting, lifestyle and behav-
ioral management, and medical nutrition
therapy. The most important diabetes-
specific component of preconception
care is the attainment of glycemic goals
prior to conception. Diabetes-specific
testing should include A1C, creatinine,
and urinary albumin-to-creatinine ratio.
Special attention should be paid to the
review of the medication list for poten-
tially harmful drugs (i.e., ACE inhibitors
[20,21], angiotensin receptor blockers
[20], and statins [22,23]). A referral for a
comprehensive eye exam is recommended.
Women with preexisting diabetic retino-
pathy will need close monitoring during
pregnancy to assess for progression of reti-
nopathy and provide treatment if indicated
(24).
Several studies have shown improved
diabetes and pregnancy outcomes
when care has been delivered from pre-
conception through pregnancy by a
multidisciplinary group focused on
improved glycemic control (25–28). One
study showed that care of preexisting
diabetes in clinics that included diabetes
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and obstetric specialists improved care
(28). However, there is no consensus on
the structure of multidisciplinary team
care for diabetes and pregnancy, and
there is a lack of evidence on the
impact on outcomes of various methods
of health care delivery (29).
GLYCEMIC TARGETS IN
PREGNANCY
Recommendations
15.7 Fasting and postprandial self-
monitoring of blood glucose
are recommended in both
gestational diabetes mellitus
and preexisting diabetes in
pregnancy to achieve optimal
glucose levels. Glucose tar-
gets are fasting plasma glu-
cose <95 mg/dL (5.3 mmol/
L) and either 1-h postprandial
glucose <140 mg/dL (7.8
mmol/L) or 2-h postprandial
glucose <120 mg/dL (6.7
mmol/L). Some women with
preexisting diabetes should
also test blood glucose pre-
prandially. B
15.8 Due to increased red blood
cell turnover, A1C is slightly
lower in normal pregnancy
than in normal nonpregnant
women. Ideally, the A1C tar-
get in pregnancy is <6% (42
mmol/mol) if this can be
achieved without significant
hypoglycemia, but the target
may be relaxed to <7% (53
mmol/mol) if necessary to
prevent hypoglycemia. B
15.9 When used in addition to
pre- and postprandial blood
glucose monitoring, continu-
ous glucose monitoring can
help to achieve A1C targets
in diabetes and pregnancy. B
15.10 When used in addition to
blood glucose monitoring tar-
geting traditional pre- and
postprandial targets, real-time
continuous glucose monitoring
can reduce macrosomia and
neonatal hypoglycemia in preg-
nancy complicated by type 1
diabetes. B
15.11 Continuous glucose monitor-
ing metrics may be used in
addition to but should not be
used as a substitute for
Table 15.1—Checklist for preconception care for women with diabetes (17,19)
Preconception education should include:
w Comprehensive nutrition assessment and recommendations for:
� Overweight/obesity or underweight
� Meal planning
� Correction of dietary nutritional deficiencies
� Caffeine intake
� Safe food preparation technique
w Lifestyle recommendations for:
� Regular moderate exercise
� Avoidance of hyperthermia (hot tubs)
� Adequate sleep
w Comprehensive diabetes self-management education
w Counseling on diabetes in pregnancy per current standards, including: natural history of
insulin resistance in pregnancy and postpartum; preconception glycemic targets; avoidance
of DKA/severe hyperglycemia; avoidance of severe hypoglycemia; progression of
retinopathy; PCOS (if applicable); fertility in patients with diabetes; genetics of diabetes;
risks to pregnancy including miscarriage, still birth, congenital malformations, macrosomia,
preterm labor and delivery, hypertensive disorders in pregnancy, etc.
w Supplementation
� Folic acid supplement (400 mg routine)
� Appropriate use of over-the-counter medications and supplements
Medical assessment and plan should include:
w General evaluation of overall health
w Evaluation of diabetes and its comorbidities and complications, including: DKA/severe
hyperglycemia; severe hypoglycemia/hypoglycemia unawareness; barriers to care;
comorbidities such as hyperlipidemia, hypertension, NAFLD, PCOS, and thyroid
dysfunction; complications such as macrovascular disease, nephropathy, neuropathy
(including autonomic bowel and bladder dysfunction), and retinopathy
w Evaluation of obstetric/gynecologic history, including history of: cesarean section,
congenital malformations or fetal loss, current methods of contraception, hypertensive
disorders of pregnancy, postpartum hemorrhage, preterm delivery, previous
macrosomia, Rh incompatibility, and thrombotic events (DVT/PE)
w Review of current medications and appropriateness during pregnancy
Screening should include:
w Diabetes complications and comorbidities, including: comprehensive foot exam;
comprehensive ophthalmologic exam; ECG in women starting at age 35 years who have
cardiac signs/symptoms or risk factors and, if abnormal, further evaluation; lipid panel;
serum creatinine; TSH; and urine protein-to-creatinine ratio
w Anemia
w Genetic carrier status (based on history):
� Cystic fibrosis
� Sickle cell anemia
� Tay-Sachs disease
� Thalassemia
� Others if indicated
w Infectious disease
� Neisseria gonorrhea/Chlamydia trachomatis
� Hepatitis C
� HIV
� Pap smear
� Syphilis
Immunizations should include:
w Rubella
w Varicella
w Hepatitis B
w Influenza
w Others if indicated
Preconception plan should include:
w Nutrition and medication plan to achieve glycemic targets prior to conception, including
appropriate implementation of monitoring, continuous glucose monitoring, and pump technology
w Contraceptive plan to prevent pregnancy until glycemic targets are achieved
w Management plan for general health, gynecologic concerns, comorbid conditions, or
complications, if present, including: hypertension, nephropathy, retinopathy; Rh
incompatibility; and thyroid dysfunction
DKA, diabetic ketoacidosis; DVT/PE, deep vein thrombosis/pulmonary embolism; ECG, elec-
trocardiogram; NAFLD, nonalcoholic fatty liver disease; PCOS, polycystic ovary syndrome;
TSH, thyroid-stimulating hormone.
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self-monitoring of blood
glucose to achieve optimal
pre- and postprandial glyce-
mic targets. E
15.12 Commonly used estimated
A1C and glucose management
indicator calculations should
not be used in pregnancy as
estimates of A1C. C
Pregnancy in women with normal glu-
cose metabolism is characterized by
fasting levels of blood glucose that are
lower than in the nonpregnant state,
due to insulin-independent glucoseuptake by the fetus and placenta, and
by mild postprandial hyperglycemia and
carbohydrate intolerance as a result of
diabetogenic placental hormones. In
patients with preexisting diabetes, gly-
cemic targets are usually achieved
through a combination of insulin admin-
istration and medical nutrition therapy.
Because glycemic targets in pregnancy
are stricter than in nonpregnant individ-
uals, it is important that women with
diabetes eat consistent amounts of car-
bohydrates to match with insulin dos-
age and to avoid hyperglycemia or
hypoglycemia. Referral to an RD/RDN is
important in order to establish a food
plan and insulin-to-carbohydrate ratio
and to determine weight gain goals.
Insulin Physiology
Given that early pregnancy is a time of
enhanced insulin sensitivity and lower
glucose levels, many women with type
1 diabetes will have lower insulin
requirements and an increased risk for
hypoglycemia (30). Around 16 weeks,
insulin resistance begins to increase,
and total daily insulin doses increase lin-
early �5% per week through week 36.
This usually results in a doubling of daily
insulin dose compared with the pre-
pregnancy requirement. The insulin
requirement levels off toward the end
of the third trimester with placental
aging. A rapid reduction in insulin
requirements can indicate the develop-
ment of placental insufficiency (31). In
women with normal pancreatic func-
tion, insulin production is sufficient to
meet the challenge of this physiological
insulin resistance and to maintain nor-
mal glucose levels. However, in women
with diabetes, hyperglycemia occurs if
treatment is not adjusted appropriately.
Glucose Monitoring
Reflecting this physiology, fasting and
postprandial monitoring of blood glucose
is recommended to achieve metabolic
control in pregnant women with diabe-
tes. Preprandial testing is also recom-
mended when using insulin pumps or
basal-bolus therapy so that premeal
rapid-acting insulin dosage can be ad-
justed. Postprandial monitoring is associ-
ated with better glycemic control and a
lower risk of preeclampsia (32–34). There
are no adequately powered randomized
trials comparing different fasting and
postmeal glycemic targets in diabetes in
pregnancy.
Similar to the targets recommended
by ACOG (upper limits are the same as
for GDM, described below) (35), the
ADA-recommended targets for women
with type 1 or type 2 diabetes are as
follows:
• Fasting glucose 70–95 mg/dL (3.9–5.3
mmol/L) and either
• One-hour postprandial glucose 110–140
mg/dL (6.1–7.8 mmol/L) or
• Two-hour postprandial glucose 100–120
mg/dL (5.6–6.7 mmol/L)
Lower limits are based on the mean
of normal blood glucose in pregnancy
(36). Lower limits do not apply to diet-
controlled type 2 diabetes. Hypoglyce-
mia in pregnancy is as defined and
treated in Recommendations 6.9–6.14
(Section 6, “Glycemic Targets,” https://
doi.org/10.2337/dc22-S006). These val-
ues represent optimal control if they
can be achieved safely. In practice, it
may be challenging for women with
type 1 diabetes to achieve these targets
without hypoglycemia, particularly women
with a history of recurrent hypoglycemia
or hypoglycemia unawareness. If women
cannot achieve these targets without
significant hypoglycemia, the ADA suggests
less stringent targets based on clinical
experience and individualization of care.
A1C in Pregnancy
In studies of women without preexisting
diabetes, increasing A1C levels within
the normal range are associated with
adverse outcomes (37). In the Hypergly-
cemia and Adverse Pregnancy Outcome
(HAPO) study, increasing levels of glyce-
mia were also associated with worsening
outcomes (38). Observational studies in
preexisting diabetes and pregnancy show
the lowest rates of adverse fetal out-
comes in association with A1C <6–6.5%
(42–48 mmol/mol) early in gestation
(4–6,39). Clinical trials have not evalu-
ated the risks and benefits of achieving
these targets, and treatment goals
should account for the risk of maternal
hypoglycemia in setting an individualized
target of <6% (42 mmol/mol) to <7%
(53 mmol/mol). Due to physiological
increases in red blood cell turnover, A1C
levels fall during normal pregnancy
(40,41). Additionally, as A1C represents
an integrated measure of glucose, it may
not fully capture postprandial hypergly-
cemia, which drives macrosomia. Thus,
although A1C may be useful, it should
be used as a secondary measure of gly-
cemic control in pregnancy, after blood
glucose monitoring.
In the second and third trimesters,
A1C <6% (42 mmol/mol) has the low-
est risk of large-for-gestational-age
infants (39,42,43), preterm delivery
(44), and preeclampsia (1,45). Taking all
of this into account, a target of <6%
(42 mmol/mol) is optimal during preg-
nancy if it can be achieved without sig-
nificant hypoglycemia. The A1C target in
a given patient should be achieved
without hypoglycemia, which, in addi-
tion to the usual adverse sequelae, may
increase the risk of low birth weight
(46). Given the alteration in red blood
cell kinetics during pregnancy and physi-
ological changes in glycemic parame-
ters, A1C levels may need to be
monitored more frequently than usual
(e.g., monthly).
Continuous Glucose Monitoring in
Pregnancy
CONCEPTT (Continuous Glucose Monitor-
ing in Pregnant Women With Type 1 Dia-
betes Trial) was a randomized controlled
trial (RCT) of real-time continuous glucose
monitoring (CGM) in addition to standard
care, including optimization of pre- and
postprandial glucose targets versus stan-
dard care for pregnant women with type
1 diabetes. It demonstrated the value of
real-time CGM in pregnancy complicated
by type 1 diabetes by showing a mild
improvement in A1C without an increase
in hypoglycemia and reductions in large-
for-gestational-age births, length of stay,
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and neonatal hypoglycemia (47). An
observational cohort study that evaluated
the glycemic variables reported using
CGM found that lower mean glucose,
lower standard deviation, and a higher
percentage of time in target range were
associated with lower risk of large-for-ges-
tational-age births and other adverse
neonatal outcomes (48). Use of the CGM-
reported mean glucose is superior to the
use of estimated A1C, glucose manage-
ment indicator, and other calculations to
estimate A1C given the changes to A1C
that occur in pregnancy (49). CGM time
in range (TIR) can be used for assessment
of glycemic control in patients with type
1 diabetes, but it does not provide action-
able data to address fasting and post-
prandial hypoglycemia or hyperglycemia.
There are no data to support the use of
TIR in women with type 2 diabetes or
GDM.
The international consensus on time
in range (50) endorses pregnancy target
ranges and goals for TIR for patients
with type 1 diabetes using CGM as
reported on the ambulatory glucose
profile; however, it does not specify the
type or accuracy of the device or need
for alarms and alerts. Selection of CGM
device should be individualized based
on patient circumstances.
• Target range 63–140 mg/dL (3.5–7.8
mmol/L): TIR, goal >70%
• Time below range (<63 mg/dL [3.5
mmol/L]), goal <4%
• Time below range (<54 mg/dL [3.0
mmol/L]), goal <1%
• Time above range (>140 mg/dL [7.8
mmol/L]), goal <25%
MANAGEMENT OF GESTATIONAL
DIABETES MELLITUS
Recommendations
15.13 Lifestyle behavior change is
an essential component of
management of gestational
diabetes mellitus and may
suffice for the treatment of
many women. Insulin should
be added if needed to
achieve glycemic targets. A
15.14 Insulin is the preferred medi-
cation for treating hypergly-
cemia in gestational diabetes
mellitus. Metformin and gly-
buride should not be used as
first-line agents, as both cross
the placenta to the fetus. A
Other oral and noninsulin
injectable glucose-loweringmedications lack long-term
safety data.
15.15 Metformin, when used to
treat polycystic ovary syn-
drome and induce ovulation,
should be discontinued by the
end of the first trimester. A
15.16 Telehealth visits for pregnant
women with gestational diabe-
tes mellitus improve outcomes
compared with standard in-
person care. A
GDM is characterized by increased risk of
large-for-gestational-age birth weight and
neonatal and pregnancy complications
and an increased risk of long-term mater-
nal type 2 diabetes and offspring abnor-
mal glucose metabolism in childhood.
These associations with maternal oral glu-
cose tolerance test (OGTT) results are
continuous with no clear inflection points
(38,51). Offspring with exposure to
untreated GDM have reduced insulin sen-
sitivity and b-cell compensation and are
more likely to have impaired glucose tol-
erance in childhood (52). In other words,
short-term and long-term risks increase
with progressive maternal hyperglycemia.
Therefore, all women should be screened
as outlined in Section 2, “Classification
and Diagnosis of Diabetes” (https://doi
.org/10.2337/dc22-S002). Although there
is some heterogeneity, many RCTs and a
Cochrane review suggest that the risk of
GDM may be reduced by diet, exercise,
and lifestyle counseling, particularly when
interventions are started during the first
or early in the second trimester (53–55).
There are no intervention trials in off-
spring of mothers with GDM. A meta-
analysis of 11 RCTs demonstrated that
metformin treatment in pregnancy
does not reduce the risk of GDM in
high-risk women with obesity, poly-
cystic ovary syndrome, or preexisting
insulin resistance (56). A meta-analy-
sis of 32 RCTs evaluating the effec-
tiveness of telehealth visits for GDM
demonstrated reduction of incidences
of cesarean delivery, neonatal hypogly-
cemia, premature rupture of mem-
branes, macrosomia, pregnancy-induced
hypertension or preeclampsia, preterm
birth, neonatal asphyxia, and polyhy-
dramnios compared with standard
in-person care (57).
Lifestyle and Behavioral Management
After diagnosis, treatment starts with
medical nutrition therapy, physical activ-
ity, and weight management, depending
on pregestational weight, as outlined in
the section below on preexisting type
2 diabetes, as well as glucose moni-
toring aiming for the targets recom-
mended by the Fifth International
Workshop-Conference on Gestational
Diabetes Mellitus (58):
• Fasting glucose <95 mg/dL (5.3
mmol/L) and either
• One-hour postprandial glucose <140
mg/dL (7.8 mmol/L) or
• Two-hour postprandial glucose <120
mg/dL (6.7 mmol/L)
Glycemic target lower limits defined
above for preexisting diabetes apply for
GDM that is treated with insulin.
Depending on the population, studies
suggest that 70–85% of women diag-
nosed with GDM under Carpenter-Cou-
stan criteria can control GDM with
lifestyle modification alone; it is antici-
pated that this proportion will be even
higher if the lower International Associ-
ation of the Diabetes and Pregnancy
Study Groups (59) diagnostic thresholds
are used.
Medical Nutrition Therapy
Medical nutrition therapy for GDM is an
individualized nutrition plan developed
between the woman and an RD/RDN
familiar with the management of GDM
(60,61). The food plan should provide
adequate calorie intake to promote fetal/
neonatal and maternal health, achieve
glycemic goals, and promote weight gain
according to 2009 Institute of Medicine
recommendations (62). There is no defin-
itive research that identifies a specific
optimal calorie intake for women with
GDM or suggests that their calorie needs
are different from those of pregnant
women without GDM. The food plan
should be based on a nutrition assess-
ment with guidance from the Dietary
Reference Intakes (DRI). The DRI for all
pregnant women recommends a mini-
mum of 175 g of carbohydrate, a mini-
mum of 71 g of protein, and 28 g of
fiber. The diet should emphasize
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monounsaturated and polyunsaturated
fats while limiting saturated fats and
avoiding trans fats. As is true for all nutri-
tion therapy in patients with diabetes,
the amount and type of carbohydrate
will impact glucose levels. The current
recommended amount of carbohydrate
is 175 g, or �35% of a 2,000-calorie diet.
Liberalizing higher quality, nutrient-dense
carbohydrates results in controlled fast-
ing/postprandial glucose, lower free fatty
acids, improved insulin action, and vascu-
lar benefits and may reduce excess infant
adiposity. Mothers who substitute fat
for carbohydrate may unintentionally
enhance lipolysis, promote elevated free
fatty acids, and worsen maternal insulin
resistance (63,64). Fasting urine ketone
testing may be useful to identify women
who are severely restricting carbohy-
drates to control blood glucose. Simple
carbohydrates will result in higher post-
meal excursions.
Physical Activity
A systematic review demonstrated
improvements in glucose control and
reductions in need to start insulin or
insulin dose requirements with an
exercise intervention. There was het-
erogeneity in the types of effective
exercise (aerobic, resistance, or both)
and duration of exercise (20–50 min/
day, 2–7 days/week of moderate
intensity) (65).
Pharmacologic Therapy
Treatment of GDM with lifestyle and insu-
lin has been demonstrated to improve
perinatal outcomes in two large random-
ized studies as summarized in a U.S. Pre-
ventive Services Task Force review (66).
Insulin is the first-line agent recom-
mended for treatment of GDM in the
U.S. While individual RCTs support limited
efficacy of metformin (67,68) and glybur-
ide (69) in reducing glucose levels for the
treatment of GDM, these agents are not
recommended as first-line treatment for
GDM because they are known to cross
the placenta and data on long-term
safety for offspring is of some concern
(35). Furthermore, glyburide and metfor-
min failed to provide adequate glycemic
control in separate RCTs in 23% and
25–28% of women with GDM, respec-
tively (70,71).
Sulfonylureas
Sulfonylureas are known to cross the
placenta and have been associated with
increased neonatal hypoglycemia. Con-
centrations of glyburide in umbilical
cord plasma are approximately 50–70%
of maternal levels (70,71). Glyburide
was associated with a higher rate of
neonatal hypoglycemia, macrosomia,
and increased neonatal abdominal cir-
cumference than insulin or metformin
in meta-analyses and systematic reviews
(72,73).
Glyburide failed to be found noninferior
to insulin based on a composite outcome
of neonatal hypoglycemia, macrosomia,
and hyperbilirubinemia (74). Long-term
safety data for offspring exposed to gly-
buride are not available (74).
Metformin
Metformin was associated with a lower
risk of neonatal hypoglycemia and less
maternal weight gain than insulin in sys-
tematic reviews (72,75–77). However,
metformin readily crosses the placenta,
resulting in umbilical cord blood levels
of metformin as high or higher than
simultaneous maternal levels (78,79). In
the Metformin in Gestational Diabetes:
The Offspring Follow-Up (MiG TOFU)
study’s analyses of 7- to 9-year-old off-
spring, the 9-year-old offspring exposed
to metformin for the treatment of GDM
in the Auckland cohort were heavier
and had a higher waist-to-height ratio
and waist circumference than those
exposed to insulin (80). This difference
was not found in the Adelaide cohort.
In two RCTs of metformin use in preg-
nancy for polycystic ovary syndrome,
follow-up of 4-year-old offspring dem-
onstrated higher BMI and increased
obesity in the offspring exposed to met-
formin (81,82). A follow-up study at
5–10 years showed that the offspring
had higher BMI, weight-to-height ratios,
waist circumferences, and a borderline
increase in fat mass (82,83). Arecent
meta-analysis concluded that metformin
exposure resulted in smaller neonates
with an acceleration of postnatal
growth, resulting in higher BMI in child-
hood (82).
Randomized, double-blind, controlled
trials comparing metformin with other
therapies for ovulation induction in
women with polycystic ovary syndrome
have not demonstrated benefit in pre-
venting spontaneous abortion or GDM
(84), and there is no evidence-based
need to continue metformin in such
patients (85–87).
There are some women with GDM
requiring medical therapy who, due to
cost, language barriers, comprehension,
or cultural influences, may not be able
to use insulin safely or effectively in
pregnancy. Oral agents may be an alter-
native in these women after a discus-
sion of the known risks and the need
for more long-term safety data in off-
spring. However, due to the potential
for growth restriction or acidosis in the
setting of placental insufficiency, met-
formin should not be used in women
with hypertension or preeclampsia or at
risk for intrauterine growth restriction
(88,89).
Insulin
Insulin use should follow the guidelines
below. Both multiple daily insulin injec-
tions and continuous subcutaneous
insulin infusion are reasonable delivery
strategies, and neither has been shown
to be superior to the other during preg-
nancy (90).
MANAGEMENT OF PREEXISTING
TYPE 1 DIABETES AND TYPE 2
DIABETES IN PREGNANCY
Insulin Use
Recommendations
15.17 Insulin should be used for
management of type 1 diabe-
tes in pregnancy. A Insulin is
the preferred agent for the
management of type 2 diabe-
tes in pregnancy. B
15.18 Either multiple daily injections
or insulin pump technology
can be used in pregnancy com-
plicated by type 1 diabetes. C
The physiology of pregnancy necessitates
frequent titration of insulin to match
changing requirements and underscores
the importance of daily and frequent
blood glucose monitoring. Due to the
complexity of insulin management in
pregnancy, referral to a specialized cen-
ter offering team-based care (with team
members including maternal-fetal medi-
cine specialist, endocrinologist or other
provider experienced in managing preg-
nancy in women with preexisting diabe-
tes, dietitian, nurse, and social worker, as
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needed) is recommended if this resource
is available.
None of the currently available human
insulin preparations have been demon-
strated to cross the placenta (90–95).
Insulins studied in RCTs are preferred
(96–99) over those studied in cohort
studies (100), which are preferred over
those studied in case reports only.
While many providers prefer insulin
pumps in pregnancy, it is not clear that
they are superior to multiple daily injec-
tions (101,102). Insulin pumps that allow
for the achievement of pregnancy
fasting and postprandial glycemic tar-
gets may reduce hypoglycemia and
allow for more aggressive prandial
dosing to achieve targets. Not all
hybrid closed-loop pumps are able to
achieve the pregnancy targets. None
of the current hybrid closed-loop insu-
lin pump systems achieve pregnancy
targets. However, predictive low glu-
cose suspend (PLGS) technology has
been shown in nonpregnant people to
be better than sensor augment tech-
nology (SAP) for reducing low glucoses
(103). It may be suited for pregnancy
because the predict low glucose
threshold for suspending insulin is in
the range of premeal and overnight
glucoses targets in pregnancy and may
allow for more aggressive prandial
dosing.
Type 1 Diabetes
Women with type 1 diabetes have an
increased risk of hypoglycemia in the first
trimester and, like all women, have
altered counterregulatory response in
pregnancy that may decrease hypoglyce-
mia awareness. Education for patients
and family members about the preven-
tion, recognition, and treatment of hypo-
glycemia is important before, during, and
after pregnancy to help to prevent and
manage the risks of hypoglycemia. Insulin
resistance drops rapidly with delivery of
the placenta.
Pregnancy is a ketogenic state, and
women with type 1 diabetes, and to a
lesser extent those with type 2 diabe-
tes, are at risk for diabetic ketoacidosis
(DKA) at lower blood glucose levels
than in the nonpregnant state. Women
with type 1 diabetes should be pre-
scribed ketone strips and receive educa-
tion on DKA prevention and detection.
DKA carries a high risk of stillbirth.
Women in DKA who are unable to eat
often require 10% dextrose with an
insulin drip to adequately meet the
higher carbohydrate demands of the
placenta and fetus in the third trimester
in order to resolve their ketosis.
Retinopathy is a special concern in
pregnancy. The necessary rapid imple-
mentation of euglycemia in the setting
of retinopathy is associated with wors-
ening of retinopathy (24).
Type 2 Diabetes
Type 2 diabetes is often associated with
obesity. Recommended weight gain dur-
ing pregnancy for women with over-
weight is 15–25 lb and for women with
obesity is 10–20 lb (62). There are no
adequate data on optimal weight gain
versus weight maintenance in women
with BMI >35 kg/m2.
Glycemic control is often easier to
achieve in women with type 2 diabetes
than in those with type 1 diabetes but
can require much higher doses of insulin,
sometimes necessitating concentrated
insulin formulations. Insulin is the pre-
ferred treatment for type 2 diabetes in
pregnancy. An RCT of metformin added
to insulin for the treatment of type 2 dia-
betes found less maternal weight gain
and fewer cesarean births. There were
fewer macrosomic neonates, but there
was a doubling of small-for-gestational-
age neonates (104). As in type 1 diabe-
tes, insulin requirements drop dramati-
cally after delivery.
The risk for associated hypertension
and other comorbidities may be as high
or higher with type 2 diabetes as with
type 1 diabetes, even if diabetes is bet-
ter controlled and of shorter apparent
duration, with pregnancy loss appearing
to be more prevalent in the third tri-
mester in women with type 2 diabetes,
compared with the first trimester in
women with type 1 diabetes (105,106).
PREECLAMPSIA AND ASPIRIN
Insulin Use
Recommendation
15.19 Women with type 1 or type
2 diabetes should be pre-
scribed low-dose aspirin
100–150 mg/day starting at
12 to 16 weeks of gestation
to lower the risk of pre-
eclampsia. E A dosage of 162
mg/day may be acceptable E;
currently, in the U.S., low-
dose aspirin is available in
81-mg tablets.
Diabetes in pregnancy is associated with
an increased risk of preeclampsia (107).
The U.S. Preventive Services Task Force
recommends the use of low-dose aspirin
(81 mg/day) as a preventive medication
at 12 weeks of gestation in women who
are at high risk for preeclampsia (108).
However, a meta-analysis and an addi-
tional trial demonstrate that low-dose
aspirin <100 mg is not effective in reduc-
ing preeclampsia. Low-dose aspirin >100
mg is required (109–111). A cost-benefit
analysis has concluded that this approach
would reduce morbidity, save lives, and
lower health care costs (112). However,
there are insufficient data regarding the
benefits of aspirin in women with preex-
isting diabetes (110). More studies are
needed to assess the long-term effects of
prenatal aspirin exposure on offspring
(113).
PREGNANCY AND DRUG
CONSIDERATIONS
Recommendations
15.20 In pregnant patients with dia-
betes and chronic hyperten-
sion, a blood pressure target
of 110–135/85 mmHg is sug-
gested in the interest of reduc-
ing the risk for accelerated
maternal hypertension A and
minimizing impaired fetal
growth. E
15.21 Potentially harmful medications
in pregnancy (i.e., ACE inhibi-
tors, angiotensin receptor block-
ers, statins) should be stopped
at conception and avoided in
sexually active women of child-
bearing age who are not using
reliable contraception. B
In normal pregnancy, blood pressure is
lower than in the nonpregnantstate.
In a pregnancy complicated by diabe-
tes and chronic hypertension, a target
goal blood pressure of 110–135/85
mmHg is suggested to reduce the risk
of uncontrolled maternal hypertension
and minimize impaired fetal growth
(114–116). The 2015 study (116)
excluded pregnancies complicated by
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preexisting diabetes, and only 6% had
GDM at enrollment. There was no dif-
ference in pregnancy loss, neonatal
care, or other neonatal outcomes
between the groups with tighter versus
less tight control of hypertension
(116).
During pregnancy, treatment with
ACE inhibitors and angiotensin recep-
tor blockers is contraindicated because
they may cause fetal renal dysplasia,
oligohydramnios, pulmonary hypopla-
sia, and intrauterine growth restriction
(20).
A large study found that after adjust-
ing for confounders, first trimester ACE
inhibitor exposure does not appear to
be associated with congenital malfor-
mations (21). However, ACE inhibitors
and angiotensin receptor blockers should
be stopped as soon as possible in the
first trimester to avoid second and third
trimester fetopathy (21). Antihyperten-
sive drugs known to be effective and
safe in pregnancy include methyldopa,
nifedipine, labetalol, diltiazem, clonidine,
and prazosin. Atenolol is not recom-
mended, but other b-blockers may be
used, if necessary. Chronic diuretic use
during pregnancy is not recommended as
it has been associated with restricted
maternal plasma volume, which may
reduce uteroplacental perfusion (117). On
the basis of available evidence, statins
should also be avoided in pregnancy (118).
See pregnancy and antihypertensive
medications in Section 10, “Cardiovascular
Disease and Risk Management” (https://
doi.org/10.2337/dc22-S010), for more
information on managing blood pressure
in pregnancy.
POSTPARTUM CARE
Recommendations
15.22 Insulin resistance decreases
dramatically immediately post-
partum, and insulin require-
ments need to be evaluated
and adjusted as they are often
roughly half the prepregnancy
requirements for the initial few
days postpartum. C
15.23 A contraceptive plan should be
discussed and implemented
with all women with diabetes
of reproductive potential. A
15.24 Screen women with a recent
history of gestational diabetes
mellitus at 4–12 weeks post-
partum, using the 75-g oral
glucose tolerance test and clin-
ically appropriate nonpreg-
nancy diagnostic criteria. B
15.25 Women with a history of ges-
tational diabetes mellitus
found to have prediabetes
should receive intensive life-
style interventions and/or
metformin to prevent diabe-
tes. A
15.26 Women with a history of
gestational diabetes mellitus
should have lifelong screen-
ing for the development of
type 2 diabetes or prediabe-
tes every 1–3 years. B
15.27 Women with a history of gesta-
tional diabetes mellitus should
seek preconception screening
for diabetes and preconception
care to identify and treat
hyperglycemia and prevent
congenital malformations. E
15.28 Postpartum care should include
psychosocial assessment and
support for self-care. E
Gestational Diabetes Mellitus
Initial Testing
Because GDM often represents previ-
ously undiagnosed prediabetes, type 2
diabetes, maturity-onset diabetes of the
young, or even developing type 1 diabe-
tes, women with GDM should be tested
for persistent diabetes or prediabetes at
4–12 weeks postpartum with a fasting
75-g OGTT using nonpregnancy criteria
as outlined in Section 2, “Classification
and Diagnosis of Diabetes” (https://doi
.org/10.2337/dc22-S002), specifically Table
2.2. In the absence of unequivocal hyper-
glycemia, a positive screen for diabetes
requires two abnormal values. If both the
fasting plasma glucose ($126 mg/dL [7.0
mmol/L]) and 2-h plasma glucose ($200
mg/dL [11.1 mmol/L]) are abnormal in a
single screening test, then the diagnosis of
diabetes is made. If only one abnormal
value in the OGTT meets diabetes criteria,
the test should be repeated to confirm
that the abnormality persists.
Postpartum Follow-up
The OGTT is recommended over A1C at
4–12 weeks postpartum because A1C
may be persistently impacted (lowered)
by the increased red blood cell turnover
related to pregnancy, by blood loss at
delivery, or by the preceding 3-month
glucose profile. The OGTT is more sensi-
tive at detecting glucose intolerance,
including both prediabetes and diabetes.
Women of reproductive age with predia-
betes may develop type 2 diabetes by
the time of their next pregnancy and will
need preconception evaluation. Because
GDM is associated with an increased life-
time maternal risk for diabetes estimated
at 50–60% (119,120), women should also
be tested every 1–3 years thereafter if
the 4–12 weeks postpartum 75-g OGTT is
normal. Ongoing evaluation may be per-
formed with any recommended glycemic
test (e.g., annual A1C, annual fasting
plasma glucose, or triennial 75-g OGTT
using nonpregnant thresholds).
Gestational Diabetes Mellitus and Type 2
Diabetes
Women with a history of GDM have a
greatly increased risk of conversion to
type 2 diabetes over time (120). Women
with GDM have a 10-fold increased risk
of developing type 2 diabetes compared
with women without GDM (119). Abso-
lute risk increases linearly through a
woman’s lifetime, being approximately
20% at 10 years, 30% at 20 years, 40%
at 30 years, 50% at 40 years, and 60% at
50 years (120). In the prospective Nurses’
Health Study II (NHS II), subsequent dia-
betes risk after a history of GDM was
significantly lower in women who fol-
lowed healthy eating patterns (121).
Adjusting for BMI attenuated this associa-
tion moderately, but not completely.
Interpregnancy or postpartum weight
gain is associated with increased risk of
adverse pregnancy outcomes in subse-
quent pregnancies (122) and earlier pro-
gression to type 2 diabetes.
Both metformin and intensive life-
style intervention prevent or delay pro-
gression to diabetes in women with
prediabetes and a history of GDM. Of
women with a history of GDM and pre-
diabetes, only 5–6 women need to be
treated with either intervention to pre-
vent one case of diabetes over 3 years
(123). In these women, lifestyle inter-
vention and metformin reduced pro-
gression to diabetes by 35% and 40%,
respectively, over 10 years compared
with placebo (124). If the pregnancy has
motivated the adoption of a healthier
diet, building on these gains to support
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https://doi.org/10.2337/dc22-S010
https://doi.org/10.2337/dc22-S010
https://doi.org/10.2337/dc22-S002
https://doi.org/10.2337/dc22-S002
weight loss is recommended in the
postpartum period.
Preexisting Type 1 and Type 2 Diabetes
Insulin sensitivity increases dramatically
with delivery of the placenta. In one
study, insulin requirements in the imme-
diate postpartum period are roughly
34% lower than prepregnancy insulin
requirements (125). Insulin sensitivity
then returns to prepregnancy levels over
the following 1–2 weeks. In women tak-
ing insulin, particular attention should be
directed to hypoglycemia prevention in
the setting of breastfeeding and erratic
sleep and eating schedules (126).
Lactation
In light of the immediate nutritional and
immunological benefits of breastfeeding
for the baby, all women, including those
with diabetes, should be supported in
attempts to breastfeed. Breastfeeding
may also confer longer-term metabolic
benefits to both mother (127) and off-
spring (128). However, lactation can
increase the risk of overnight hypoglyce-
mia, and insulin dosing may need to be
adjusted.
Contraception
A major barrier to effective preconcep-
tion care is the fact that the majority of
pregnancies are unplanned. Planningpregnancy is critical in women with pre-
existing diabetes due to the need for pre-
conception glycemic control to prevent
congenital malformations and reduce the
risk of other complications. Therefore, all
women with diabetes of childbearing
potential should have family planning
options reviewed at regular intervals to
make sure that effective contraception is
implemented and maintained. This applies
to women in the immediate postpartum
period. Women with diabetes have the
same contraception options and recom-
mendations as those without diabetes.
Long-acting, reversible contraception may
be ideal for many women. The risk of an
unplanned pregnancy outweighs the risk
of any given contraception option.
References
1. Dabelea D, Hanson RL, Lindsay RS, et al.
Intrauterine exposure to diabetes conveys risks for
type 2 diabetes and obesity: a study of discordant
sibships. Diabetes 2000;49:2208–2211
2. Holmes VA, Young IS, Patterson CC, et al.;
Diabetes and Pre-eclampsia Intervention Trial
Study Group. Optimal glycemic control, pre-
eclampsia, and gestational hypertension in
women with type 1 diabetes in the diabetes and
pre-eclampsia intervention trial. Diabetes Care
2011;34:1683–1688
3. Guerin A, Nisenbaum R, Ray JG. Use of
maternal GHb concentration to estimate the risk
of congenital anomalies in the offspring of
women with prepregnancy diabetes. Diabetes
Care 2007;30:1920–1925
4. Jensen DM, Korsholm L, Ovesen P, et al. Peri-
conceptional A1C and risk of serious adverse
pregnancy outcome in 933 women with type 1
diabetes. Diabetes Care 2009;32:1046–1048
5. Nielsen GL, Møller M, Sørensen HT. HbA1c in
early diabetic pregnancy and pregnancy
outcomes: a Danish population-based cohort
study of 573 pregnancies in women with type 1
diabetes. Diabetes Care 2006;29:2612–2616
6. Suhonen L, Hiilesmaa V, Teramo K. Glycaemic
control during early pregnancy and fetal
malformations in women with type I diabetes
mellitus. Diabetologia 2000;43:79–82
7. Ludvigsson JF, Neovius M, S€oderling J, et al.
Maternal glycemic control in type 1 diabetes and
the risk for preterm birth: a population-based
cohort study. Ann InternMed 2019;170:691–701
8. Wahabi HA, Fayed A, Esmaeil S, et al.
Systematic review and meta-analysis of the
effectiveness of pre-pregnancy care for women
with diabetes for improving maternal and
perinatal outcomes. PLoS One 2020;15:e0237571
9. Charron-Prochownik D, Sereika SM, Becker D,
et al. Long-term effects of the booster-enhanced
READY-Girls preconception counseling program
on intentions and behaviors for family planning
in teens with diabetes. Diabetes Care 2013;36:
3870–3874
10. Peterson C, Grosse SD, Li R, et al.
Preventable health and cost burden of adverse
birth outcomes associated with pregestational
diabetes in the United States. Am J Obstet
Gynecol 2015;212:74.e1–74.e9
11. Britton LE, Hussey JM, Berry DC, Crandell JL,
Brooks JL, Bryant AG. Contraceptive use among
women with prediabetes and diabetes in a US
national sample. J Midwifery Womens Health
2019;64:36–45
12. Morris JR, Tepper NK. Description and
comparison of postpartum use of effective
contraception among women with and without
diabetes. Contraception 2019;100:474–479
13. Goldstuck ND, Steyn PS. The intrauterine
device in women with diabetes mellitus type i
and ii: a systematic review. ISRN Obstet Gynecol
2013;2013:814062
14. Wu JP, Moniz MH, Ursu AN. Long-acting
reversible contraception—highly efficacious,
safe, and underutilized. JAMA 2018;320:397–398
15. American College of Obstetricians and
Gynecologists’ Committee on Practice Bulletins—
Obstetrics. ACOG Practice Bulletin No. 201:
Pregestational diabetes mellitus. Obstet Gynecol
2018;132:e228–e248
16. Charron-Prochownik D, Downs J. Diabetes
and Reproductive Health for Girls. Alexandria,VA,
American Diabetes Association, 2016
17. American College of Obstetricians and
Gynecologists’ Committee on Gynecologic
Practice; American Society for Reproductive
Medicine. ACOG Committee Opinion No. 762:
Prepregnancy counseling. Obstet Gynecol
2019;133:e78–e89
18. Alexander EK, Pearce EN, Brent GA, et al.
2017 guidelines of the American Thyroid
Association for the diagnosis andmanagement of
thyroid disease during pregnancy and the
postpartum.Thyroid 2017;27:315–389
19. Ramos DE. Preconception health: changing
the paradigm on well-woman health. Obstet
Gynecol Clin North Am 2019;46:399–408
20. BulloM,Tschumi S, Bucher BS, Bianchetti MG,
Simonetti GD. Pregnancy outcome following
exposure to angiotensin-converting enzyme
inhibitors or angiotensin receptor antagonists: a
systematic review. Hypertension 2012;60:444–450
21. Bateman BT, Patorno E, Desai RJ, et al.
Angiotensin-converting enzyme inhibitors and
the risk of congenital malformations. Obstet
Gynecol 2017;129:174–184
22. Taguchi N, Rubin ET, Hosokawa A, et al.
Prenatal exposure to HMG-CoA reductase
inhibitors: effects on fetal and neonatal
outcomes. Reprod Toxicol 2008;26:175–177
23. Bateman BT, Hernandez-Diaz S, Fischer MA,
et al. Statins and congenital malformations:
cohort study. BMJ 2015;350:h1035
24. Chew EY, Mills JL, Metzger BE, et al.;
National Institute of Child Health and Human
Development Diabetes in Early Pregnancy Study.
Metabolic control and progression of
retinopathy. The Diabetes in Early Pregnancy
Study. Diabetes Care 1995;18:631–637
25. McElvy SS, Miodovnik M, Rosenn B, et al. A
focused preconceptional and early pregnancy
program in women with type 1 diabetes reduces
perinatal mortality and malformation rates to
general population levels. J Matern Fetal Med
2000;9:14–20
26. Murphy HR, Roland JM, Skinner TC, et al.
Effectiveness of a regional prepregnancy care
program in women with type 1 and type 2
diabetes: benefits beyond glycemic control.
Diabetes Care 2010;33:2514–2520
27. Elixhauser A, Weschler JM, Kitzmiller JL,
et al. Cost-benefit analysis of preconception care
for women with established diabetes mellitus.
Diabetes Care 1993;16:1146–1157
28. Owens LA, Avalos G, Kirwan B, Carmody L,
Dunne F. ATLANTIC DIP: closing the loop: a
change in clinical practice can improve outcomes
for women with pregestational diabetes.
Diabetes Care 2012;35:1669–1671
29. Taylor C, McCance DR, Chappell L, et al.
Implementation of guidelines for multidisciplinary
team management of pregnancy in women with
pre-existing diabetes or cardiac conditions: results
from a UK national survey. BMC Pregnancy
Childbirth 2017;17:434
30. Garc�ıa-Patterson A, Gich I, Amini SB,
Catalano PM, de Leiva A, Corcoy R. Insulin
requirements throughout pregnancy in women
with type 1 diabetes mellitus: three changes of
direction. Diabetologia 2010;53:446–451
31. Padmanabhan S, Lee VW, Mclean M, et al.
The association of falling insulin requirements
with maternal biomarkers and placental
dysfunction: a prospective study of women with
preexisting diabetes in pregnancy. Diabetes Care
2017;40:1323–1330
32. Manderson JG, Patterson CC, Hadden DR,
Traub AI, Ennis C, McCance DR. Preprandial
versus postprandial blood glucose monitoring in
type 1 diabetic pregnancy: a randomized
S240 Management of Diabetes in Pregnancy Diabetes Care Volume 45, Supplement 1, January 2022
D
ow
nloaded from
 http://diabetesjournals.org/care/article-pdf/45/Supplem
ent_1/S232/636911/dc22s015.pdf by guest on 31 August 2022
controlled clinical trial. Am J Obstet Gynecol
2003;189:507–512
33. de Veciana M, Major CA, Morgan MA, et al.
Postprandial versus preprandial blood glucose
monitoring in women with gestational diabetes
mellitus requiring insulin therapy. N Engl J Med
1995;333:1237–1241
34. Jovanovic-Peterson L, Peterson CM, Reed GF,
et al.; National Institute of Child Health and
Human Development—Diabetes in Early
Pregnancy Study. Maternal postprandial glucose
levels and infant birth weight: the Diabetes in
Early Pregnancy Study. Am J Obstet Gynecol
1991;164:103–111
35. Committee on Practice Bulletins—Obstetrics.
ACOG Practice Bulletin No. 190: Gestational
diabetes mellitus. Obstet Gynecol 2018;131:
e49–e64
36. Hernandez TL, Friedman JE, Van Pelt RE,
Barbour LA. Patterns of glycemia in normalpregnancy: should the current therapeutic targets
be challenged? Diabetes Care 2011;34:1660–1668
37. Ho Y-R, Wang P, Lu M-C, Tseng S-T, Yang C-P,
Yan Y-H. Associations of mid-pregnancy HbA1c
with gestational diabetes and risk of adverse
pregnancy outcomes in high-risk Taiwanese
women. PLoS One 2017;12:e0177563
38. Metzger BE, Lowe LP, Dyer AR, et al.; HAPO
Study Cooperative Research Group. Hyper-
glycemia and adverse pregnancy outcomes. N
Engl J Med 2008;358:1991–2002
39. Maresh MJA, Holmes VA, Patterson CC,
et al.; Diabetes and Pre-eclampsia Intervention
Trial Study Group. Glycemic targets in the second
and third trimester of pregnancy for women with
type 1 diabetes. Diabetes Care 2015;38:34–42
40. Nielsen LR, Ekbom P, Damm P, et al. HbA1c
levels are significantly lower in early and late
pregnancy. Diabetes Care 2004;27:1200–1201
41. Mosca A, Paleari R, Dalfr�a MG, et al.
Reference intervals for hemoglobin A1c in
pregnant women: data from an Italian
multicenter study. Clin Chem 2006;52:1138–1143
42. Hummel M, Marienfeld S, Huppmann M,
et al. Fetal growth is increased by maternal type
1 diabetes and HLA DR4-related gene
interactions. Diabetologia 2007;50:850–858
43. Cyganek K, Skupien J, Katra B, et al. Risk of
macrosomia remains glucose-dependent in a
cohort of women with pregestational type 1
diabetes and good glycemic control. Endocrine
2017;55:447–455
44. Abell SK, Boyle JA, de Courten B, et al.
Impact of type 2 diabetes, obesity and glycaemic
control on pregnancy outcomes. Aust N Z J
Obstet Gynaecol 2017;57:308–314
45. Temple RC, Aldridge V, Stanley K, Murphy
HR. Glycaemic control throughout pregnancy and
risk of pre-eclampsia in women with type I
diabetes. BJOG 2006;113:1329–1332
46. Combs CA, Gunderson E, Kitzmiller JL, Gavin
LA, Main EK. Relationship of fetal macrosomia to
maternal postprandial glucose control during
pregnancy. Diabetes Care 1992;15:1251–1257
47. Feig DS, Donovan LE, Corcoy R, et al.;
CONCEPTT Collaborative Group. Continuous
glucose monitoring in pregnant women with
type 1 diabetes (CONCEPTT): a multicentre
international randomised controlled trial. Lancet
2017;390:2347–2359
48. Kristensen K, €Ogge LE, Sengpiel V, et al.
Continuous glucose monitoring in pregnant
women with type 1 diabetes: an observational
cohort study of 186 pregnancies. Diabetologia
2019;62:1143–1153
49. Law GR, Gilthorpe MS, Secher AL, et al.
Translating HbA1c measurements into estimated
average glucose values in pregnant women with
diabetes. Diabetologia 2017;60:618–624
50. Battelino T, Danne T, Bergenstal RM, et al.
Clinical targets for continuous glucosemonitoring
data interpretation: recommendations from the
international consensus on time in range.
Diabetes Care 2019;42:1593–1603
51. Scholtens DM, Kuang A, Lowe LP, et al.;
HAPO Follow-up Study Cooperative Research
Group; HAPO Follow-Up Study Cooperative
Research Group. Hyperglycemia and Adverse
Pregnancy Outcome Follow-up Study (HAPO
FUS): maternal glycemia and childhood glucose
metabolism. Diabetes Care 2019;42:381–392
52. Lowe WL Jr, Scholtens DM, Kuang A, et al.;
HAPO Follow-up Study Cooperative Research
Group. Hyperglycemia and Adverse Pregnancy
Outcome Follow-up Study (HAPO FUS): maternal
gestational diabetes mellitus and childhood glucose
metabolism. Diabetes Care 2019;42:372–380
53. Koivusalo SB, R€on€o K, Klemetti MM, et al.
Gestational diabetes mellitus can be prevented
by lifestyle intervention: the Finnish Gestational
Diabetes Prevention Study (RADIEL): a
randomized controlled trial. Diabetes Care
2016;39:24–30
54. Wang C, Wei Y, Zhang X, et al. A randomized
clinical trial of exercise during pregnancy to prevent
gestational diabetes mellitus and improve
pregnancy outcome in overweight and obese
pregnant women. Am J Obstet Gynecol 2017;216:
340–351
55. Griffith RJ, Alsweiler J, Moore AE, et al.
Interventions to prevent women from developing
gestational diabetes mellitus: an overview of
Cochrane Reviews. Cochrane Database Syst Rev
2020;6:CD012394
56. Doi SAR, Furuya-Kanamori L, Toft E, et al.
Metformin in pregnancy to avert gestational
diabetes in women at high risk: meta-analysis of
randomized controlled trials. Obes Rev
2020;21:e12964
57. Xie W, Dai P, Qin Y, Wu M, Yang B, Yu X.
Effectiveness of telemedicine for pregnant
women with gestational diabetes mellitus: an
updated meta-analysis of 32 randomized
controlled trials with trial sequential analysis.
BMC Pregnancy Childbirth 2020;20:198
58. Metzger BE, Buchanan TA, Coustan DR, et al.
Summary and recommendations of the Fifth
International Workshop-Conference on Gestational
Diabetes Mellitus. Diabetes Care 2007;30(Suppl.
2):S251–S260
59. Mayo K, Melamed N, Vandenberghe H,
Berger H. The impact of adoption of the
International Association of Diabetes in
Pregnancy Study Group criteria for the screening
and diagnosis of gestational diabetes. Am J
Obstet Gynecol 2015;212:224.e1–224.e9
60. Han S, Crowther CA, Middleton P, Heatley E.
Different types of dietary advice for women with
gestational diabetes mellitus. Cochrane Database
Syst Rev 2013;3:CD009275
61. Viana LV, Gross JL, Azevedo MJ. Dietary
intervention in patients with gestational diabetes
mellitus: a systematic review and meta-analysis
of randomized clinical trials on maternal and
newborn outcomes. Diabetes Care 2014;37:
3345–3355
62. Institute of Medicine and National Research
Council. Weight Gain During Pregnancy:
Reexamining the Guidelines. Washington, D.C.,
National Academies Press, 2009
63. Hernandez TL, Mande A, Barbour LA.
Nutrition therapy within and beyond gestational
diabetes. Diabetes Res Clin Pract 2018;145:39–50
64. Hernandez TL, Van Pelt RE, Anderson MA,
et al. A higher-complex carbohydrate diet in
gestational diabetes mellitus achieves glucose
targets and lowers postprandial lipids: a
randomized crossover study. Diabetes Care
2014;37:1254–1262
65. Laredo-Aguilera JA, Gallardo-Bravo M,
Rabanales-Sotos JA, Cobo-Cuenca AI, Carmona-
Torres JM. Physical activity programs during
pregnancy are effective for the control of
gestational diabetes mellitus. Int J Environ Res
Public Health 2020;17:E6151
66. Hartling L, Dryden DM, Guthrie A, Muise M,
Vandermeer B, Donovan L. Benefits and harms of
treating gestational diabetes mellitus: a
systematic review and meta-analysis for the U.S.
Preventive Services Task Force and the National
Institutes of Health Office of Medical Applications
of Research. Ann InternMed 2013;159:123–129
67. Rowan JA, Hague WM, Gao W, Battin MR;
MiG Trial Investigators. Metformin versus insulin
for the treatment of gestational diabetes. N Engl
J Med 2008;358:2003–2015
68. Gui J, Liu Q, Feng L. Metformin vs insulin in
themanagement of gestational diabetes: a meta-
analysis. PLoS One 2013;8:e64585
69. Langer O, Conway DL, Berkus MD, Xenakis
EM-J, Gonzales O. A comparison of glyburide and
insulin in women with gestational diabetes
mellitus. N Engl J Med 2000;343:1134–1138
70. Hebert MF, Ma X, Naraharisetti SB, et al.;
Obstetric-Fetal Pharmacology Research Unit
Network. Are we optimizing gestational diabetes
treatment with glyburide? The pharmacologic
basis for better clinical practice. Clin Pharmacol
Ther 2009;85:607–614
71. Malek R, Davis SN. Pharmacokinetics,
efficacy and safety of glyburide for treatment of
gestational diabetes mellitus. Expert Opin Drug
Metab Toxicol 2016;12:691–699
72. Balsells M, Garc�ıa-Patterson A, Sol�a I, Roqu�e
M, Gich I, Corcoy R. Glibenclamide, metformin,
and insulin for the treatment of gestational
diabetes: a systematic review and meta-analysis.
BMJ 2015;350:h102
73. Tarry-Adkins JL, Aiken CE, Ozanne SE.
Comparative impact of pharmacological
treatments for gestational diabetes on neonatal
anthropometry independent of maternal
glycaemic control: a systematic review and meta-
analysis. PLoSMed 2020;17:e1003126
74. S�enat M-V, Affres H, Letourneau A, et al.;
Groupe de Recherche en Obst�etrique et
Gyn�ecologie (GROG). Effect of glyburide vs
subcutaneous insulin on perinatal complications
among women with gestational diabetes: a
randomized clinical trial. JAMA 2018;319:
1773–1780
75.Silva JC, Pacheco C, Bizato J, de Souza BV,
Ribeiro TE, Bertini AM. Metformin compared
with glyburide for the management of
gestational diabetes. Int J Gynaecol Obstet
2010;111:37–40
care.diabetesjournals.org Management of Diabetes in Pregnancy S241
D
ow
nloaded from
 http://diabetesjournals.org/care/article-pdf/45/Supplem
ent_1/S232/636911/dc22s015.pdf by guest on 31 August 2022
76. Nachum Z, Zafran N, Salim R, et al. Glyburide
versus metformin and their combination for the
treatment of gestational diabetes mellitus: a
randomized controlled study. Diabetes Care
2017;40:332–337
77. Jiang Y-F, Chen X-Y, Ding T, Wang X-F, Zhu Z-
N, Su S-W. Comparative efficacy and safety of
OADs in management of GDM: network meta-
analysis of randomized controlled trials. J Clin
Endocrinol Metab 2015;100:2071–2080
78. Vanky E, Zahlsen K, Spigset O, Carlsen SM.
Placental passage of metformin in women with
polycystic ovary syndrome. Fertil Steril 2005;83:
1575–1578
79. Charles B, Norris R, Xiao X, Hague W.
Population pharmacokinetics of metformin in
late pregnancy.Ther DrugMonit 2006;28:67–72
80. Rowan JA, Rush EC, Plank LD, et al.
Metformin in gestational diabetes: the offspring
follow-up (MiG TOFU): body composition and
metabolic outcomes at 7-9 years of age. BMJ
Open Diabetes Res Care 2018;6:e000456
81. Hanem LGE, Stridsklev S, J�ul�ıusson PB, et al.
Metformin use in PCOS pregnancies increases
the risk of offspring overweight at 4 years of age:
follow-up of two RCTs. J Clin Endocrinol Metab
2018;103:1612–1621
82. Tarry-Adkins JL, Aiken CE, Ozanne SE.
Neonatal, infant, and childhood growth following
metformin versus insulin treatment for
gestational diabetes: a systematic review and
meta-analysis. PLoSMed 2019;16:e1002848
83. Hanem LGE, Salvesen Ø, Juliusson PB, et al.
Intrauterine metformin exposure and offspring
cardiometabolic risk factors (PedMet study): a 5-
10 year follow-up of the PregMet randomised
controlled trial. Lancet Child Adolesc Health
2019;3:166–174
84. Vanky E, Stridsklev S, Heimstad R, et al.
Metformin versus placebo from first trimester to
delivery in polycystic ovary syndrome: a
randomized, controlled multicenter study. J Clin
Endocrinol Metab 2010;95:E448–E455
85. Legro RS, Barnhart HX, Schlaff WD, et al.;
Cooperative Multicenter Reproductive Medicine
Network. Clomiphene, metformin, or both for
infertility in the polycystic ovary syndrome. N
Engl J Med 2007;356:551–566
86. Palomba S, Orio F Jr, Falbo A, et al.
Prospective parallel randomized, double-blind,
double-dummy controlled clinical trial comparing
clomiphene citrate and metformin as the first-
line treatment for ovulation induction in
nonobese anovulatory women with polycystic
ovary syndrome. J Clin Endocrinol Metab
2005;90:4068–4074
87. Palomba S, Orio F Jr, Nardo LG, et al.
Metformin administration versus laparoscopic
ovarian diathermy in clomiphene citrate-resistant
women with polycystic ovary syndrome: a
prospective parallel randomized double-blind
placebo-controlled trial. J Clin Endocrinol Metab
2004;89:4801–4809
88. Barbour LA, Scifres C, Valent AM, et al. A
cautionary response to SMFM statement:
pharmacological treatment of gestational diabetes.
Am J Obstet Gynecol 2018;219:367.e1–367.e7
89. Barbour LA, Feig DS. Metformin for
gestational diabetes mellitus: progeny, perspective,
and a personalized approach. Diabetes Care
2019;42:396–399
90. Farrar D, Tuffnell DJ, West J, West HM.
Continuous subcutaneous insulin infusion versus
multiple daily injections of insulin for pregnant
women with diabetes. Cochrane Database Syst
Rev 2016;6:CD005542
91. Pollex EK, Feig DS, Lubetsky A, Yip PM, Koren
G. Insulin glargine safety in pregnancy: a
transplacental transfer study. Diabetes Care
2010;33:29–33
92. Holcberg G, Tsadkin-Tamir M, Sapir O, et al.
Transfer of insulin lispro across the human
placenta. Eur J Obstet Gynecol Reprod Biol
2004;115:117–118
93. Boskovic R, Feig DS, Derewlany L, Knie B,
Portnoi G, Koren G. Transfer of insulin lispro
across the human placenta: in vitro perfusion
studies. Diabetes Care 2003;26:1390–1394
94. McCance DR, Damm P, Mathiesen ER, et al.
Evaluation of insulin antibodies and placental
transfer of insulin aspart in pregnant women
with type 1 diabetes mellitus. Diabetologia
2008;51:2141–2143
95. Suffecool K, Rosenn B, Niederkofler EE, et al.
Insulin detemir does not cross the human
placenta. Diabetes Care 2015;38:e20–e21
96. Mathiesen ER, Hod M, Ivanisevic M, et al.;
Detemir in Pregnancy Study Group. Maternal
efficacy and safety outcomes in a randomized,
controlled trial comparing insulin detemir with
NPH insulin in 310 pregnant women with type 1
diabetes. Diabetes Care 2012;35:2012–2017
97. Hod M, Mathiesen ER, Jovanovi�c L, et al. A
randomized trial comparing perinatal outcomes
using insulin detemir or neutral protamine
Hagedorn in type 1 diabetes. J Matern Fetal
Neonatal Med 2014;27:7–13
98. Hod M, Damm P, Kaaja R, et al.; Insulin
Aspart Pregnancy Study Group. Fetal and
perinatal outcomes in type 1 diabetes pregnancy:
a randomized study comparing insulin aspart
with human insulin in 322 subjects. Am J Obstet
Gynecol 2008;198:186.e1–186.e7
99. Persson B, Swahn M-L, Hjertberg R, et al.
Insulin lispro therapy in pregnancies complicated
by type 1 diabetes mellitus. Diabetes Res Clin
Pract 2002;58:115–121
100. Pollex E, Moretti ME, Koren G, Feig DS.
Safety of insulin glargine use in pregnancy: a
systematic review and meta-analysis. Ann
Pharmacother 2011;45:9–16
101. Carta Q, Meriggi E, Trossarelli GF, et al.
Continuous subcutaneous insulin infusion versus
intensive conventional insulin therapy in type I
and type II diabetic pregnancy. Diabete Metab
1986;12:121–129
102. Kernaghan D, Farrell T, Hammond P, Owen
P. Fetal growth in women managed with insulin
pump therapy compared to conventional insulin.
Eur J Obstet Gynecol Reprod Biol 2008;137:
47–49
103. Forlenza GP, Li Z, Buckingham BA, et al.
Predictive low-glucose suspend reduces hy-
poglycemia in adults, adolescents, and children
with type 1 diabetes in an at-home randomized
crossover study: results of the PROLOG trial.
Diabetes Care 2018;41:2155–2161
104. Feig DS, Donovan LE, Zinman B, et al.; MiTy
Collaborative Group. Metformin in women with
type 2 diabetes in pregnancy (MiTy): a
multicentre, international, randomised, placebo-
controlled trial. Lancet Diabetes Endocrinol
2020;8:834–844
105. Clausen TD, Mathiesen E, Ekbom P,
Hellmuth E, Mandrup-Poulsen T, Damm P. Poor
pregnancy outcome in women with type 2
diabetes. Diabetes Care 2005;28:323–328
106. Cundy T, Gamble G, Neale L, et al.
Differing causes of pregnancy loss in type 1
and type 2 diabetes. Diabetes Care 2007;
30:2603–2607
107. Duckitt K, Harrington D. Risk factors for
pre-eclampsia at antenatal booking: systematic
review of controlled studies. BMJ 2005;330:565
108. Henderson JT, Whitlock EP, O’Conner E,
Senger CA, Thompson JH, Rowland MG. Low-
dose aspirin for the prevention of morbidity
and mortality from preeclampsia: a systematic
evidence review for the U.S. Preventive
Services Task Force. Rockville, MD, Agency for
Healthcare Research and Quality, 2014.
(Evidence Syntheses, No. 112). Accessed 17
October 2021. Available from https://www
.ncbi.nlm.nih.gov/books/NBK196392/
109. Roberge S, Bujold E, Nicolaides KH. Aspirin
for the prevention of preterm and term
preeclampsia: systematic review andmetaanalysis.
Am J Obstet Gynecol 2018;218:287–293.e1
110. Rolnik DL, Wright D, Poon LC, et al. Aspirin
versus placebo in pregnancies at high risk for
preterm preeclampsia. N Engl J Med
2017;377:613–622
111. Hoffman MK, Goudar SS, Kodkany BS,
et al.; ASPIRIN Study Group. Low-dose aspirin for
the prevention of preterm delivery in nulliparous
women with a singleton pregnancy (ASPIRIN): a
randomised, double-blind, placebo-controlled
trial. Lancet 2020;395:285–293
112. Werner EF, Hauspurg AK, Rouse DJ. A
Cost-benefit analysis of low-dose aspirin
prophylaxis for the prevention of preeclampsia
in the United States. Obstet Gynecol
2015;126:1242–1250
113. Voutetakis A, Pervanidou P, Kanaka-
Gantenbein C. Aspirinfor the prevention of
preeclampsia and potential consequences for
fetal brain development. JAMA Pediatr 2019;
173:619–620
114. Brown MA, Magee LA, Kenny LC, et al.;
International Society for the Study of
Hypertension in Pregnancy (ISSHP). Hypertensive
disorders of pregnancy: ISSHP classification,
diagnosis, and management recommendations for
international practice. Hypertension 2018;72:24–43
115. American College of Obstetricians and
Gynecologists’ Committee on Practice Bulletins—
Obstetrics. ACOG Practice Bulletin No. 203:
Chronic hypertension in pregnancy. Obstet
Gynecol 2019;133:e26–e50
116. Magee LA, von Dadelszen P, Rey E, et al.
Less-tight versus tight control of hypertension
in pregnancy. N Engl J Med 2015;372:407–417
117. Sibai BM. Treatment of hypertension in
pregnant women. N Engl J Med 1996;335:257–265
118. Kazmin A, Garcia-Bournissen F, Koren G.
Risks of statin use during pregnancy: a systematic
review. J Obstet Gynaecol Can 2007;29:906–908
119. Vounzoulaki E, Khunti K, Abner SC, Tan BK,
Davies MJ, Gillies CL. Progression to type 2
diabetes in women with a known history of
gestational diabetes: systematic review and
meta-analysis. BMJ 2020;369:m1361
S242 Management of Diabetes in Pregnancy Diabetes Care Volume 45, Supplement 1, January 2022
D
ow
nloaded from
 http://diabetesjournals.org/care/article-pdf/45/Supplem
ent_1/S232/636911/dc22s015.pdf by guest on 31 August 2022
https://www.ncbi.nlm.nih.gov/books/NBK196392/
https://www.ncbi.nlm.nih.gov/books/NBK196392/
120. Li Z, Cheng Y, Wang D, et al. Incidence rate
of type 2 diabetes mellitus after gestational
diabetes mellitus: a systematic review and meta-
analysis of 170,139 women. J Diabetes Res
2020;2020:3076463
121. Tobias DK, Hu FB, Chavarro J, Rosner B,
Mozaffarian D, Zhang C. Healthful dietary
patterns and type 2 diabetes mellitus risk
among women with a history of gestational
diabetes mellitus. Arch Intern Med 2012;
172:1566–1572
122. Villamor E, Cnattingius S. Interpregnancy
weight change and risk of adverse pregnancy
outcomes: a population-based study. Lancet
2006;368:1164–1170
123. Ratner RE, Christophi CA, Metzger BE,
et al.; Diabetes Prevention Program Research
Group. Prevention of diabetes in women with a
history of gestational diabetes: effects of
metformin and lifestyle interventions. J Clin
Endocrinol Metab 2008;93:4774–4779
124. Aroda VR, Christophi CA, Edelstein SL, et al.;
Diabetes Prevention Program Research Group. The
effect of lifestyle intervention and metformin on
preventing or delaying diabetes among women with
and without gestational diabetes: the Diabetes
Prevention Program outcomes study 10-year follow-
up. J Clin EndocrinolMetab 2015;100:1646–1653
125. Achong N, Duncan EL, McIntyre HD,
Callaway L. Peripartum management of glycemia
in women with type 1 diabetes. Diabetes Care
2014;37:364–371
126. Riviello C, Mello G, Jovanovic LG.
Breastfeeding and the basal insulin requirement
in type 1 diabetic women. Endocr Pract 2009;15:
187–193
127. Stuebe AM, Rich-Edwards JW, Willett WC,
Manson JE, Michels KB. Duration of lactation and
incidence of type 2 diabetes. JAMA 2005;294:
2601–2610
128. Pereira PF, Alfenas R de CG, Ara�ujo
RMA. Does breastfeeding influence the risk of
developing diabetes mellitus in children? A
review of current evidence. J Pediatr (Rio J)
2014;90:7–15
care.diabetesjournals.org Management of Diabetes in Pregnancy S243
D
ow
nloaded from
 http://diabetesjournals.org/care/article-pdf/45/Supplem
ent_1/S232/636911/dc22s015.pdf by guest on 31 August 2022